Our previous studies have shown that there may be a functional relationship between benzodiazepine (BZ) receptor stimulation and alterations in calcium flux. Nifedipine, a calcium channel blocker, prevents the sleep-inducing effects of flurazepam in rats. Conversely, BAY K 8644, a calcium channel agonist, potentiates the effects of flurazepam on sleep. However, as we reported last year, experimental models for the anticonvulsant and anxiolytic effects of BZ's are not affected by calcium channel antagonists, indicating that calcium channels may have a more important role in sleep induction than in other actions of BZ's. The sleep- inducing effects of pentobarbital were not sensitive to inhibition by nifedipine, indicating that barbiturates may cause sleep through a mechanism that does not require changes in calcium flux. Since pentobarbital causes changes in chloride ion flux, a second mechanism for sleep induction might involve a chloride channel. To expand this line of investigation, this year we studied the effects of sleep of two steroids, which enhance chloride uptake into synaptoneurosomes in a manner similar to barbiturates. The two steroids, 3alpha, 5alpha-tetrahydrocorticosterone (THDOC) and 3alpha-hydroxy-5alpha-dihydroprogesterone (OH- DHP), are endogenously occurring ring A metabolites of corticosterone and progesterone. Since THDOC and OH-DHP not only alter chloride flux but also enhance the binding of (3H)flunitrazepam to brain membranes, we studied the effects on sleep in rats of 5 and 10 mg/kg of the steroids alone and in combination with a low dose of flurazepam. THDOC, but not OH- DHP, had potent dose-dependent sleep-inducing properties and increased nonREM sleep, but did not affect REM sleep. Flurazepam had a similar hypnotic effect but additionally reduced REM sleep. There were no significant interactions between THDOC and flurazepam.